Significance of MT specific CD4+T cell activation markers in monitoring anti-tuberculosis therapy in patients with smear-negative and smear-positive pulmonary tuberculosis

LIU Fang; DU Qing; DENG Gaoyan; ZHOU Liang; SU Qian; PENG Zhou; WANG Juan

doi:10.3969/j.issn.1007-8134.2025.05.006

Abstract：Objective To investigate the significance of the expression of CD38,human leukocyte antigen DR(HLA-DR)and Ki-67 on the surface activation molecules of Mycobacterium tuberculosis(MT)specific CD154+CD4+T cells in differentiating smear-negative and smear-positive pulmonary tuberculosis(PTB)and monitoring anti-tuberculosis therapy.Methods A total of 100 newly treated PTB patients admitted to the hospital from January 2021 to June 2023 were selected as the study objects,and further divided into the smear negative group(n=48)and the smear positive group(n=52).All patients received standard anti-tuberculosis therapy.Sputum culture was detected after 2 months of intensive treatment.CD4+T cells from peripheral blood mononuclear cells responding to purified Mycobacterium tuberculosis purified protein derivative(PPD)or 6kD early secretory antigenic target/culture filtrate protein10(ESAT-6/CFP-10)were analyzed.Based on the expression profiles of the proliferation marker nuclear-associatedantigenki-67(Ki-67),the activation marker differentiation cluster of differentiation(CD38),and human leukocyte antigen DR(HLA-DR),the activation status of tuberculosis antigen-reactive T cells identified by the surface expression of CD154+was evaluated.Results There was no statistically significant difference in the proportion of PPD reactive CD154+CD4+T cells between the negative and positive groups(P>0.05);The proportion of ESAT-6/CFP-10 reactive CD154+CD4+T cells in the smear-positive group was higher than that in the smear-negative group,and the difference was statistically significant(P<0.05).However,in the working characteristic curve of the subjects,the area under the curve for distinguishing the proportion of ESAT-6/CFP-10 reactive CD154+CD4+T cells in the positive group was only 0.601.In addition,the proportion of CD38+,HLA DR+or Ki-67+PPD or ESAT-6/CFP-10 specific CD154+CD4+T cells in the smear-positive group was significantly higher than that in the smear-negative group,and the difference was statistically significant(P<0.05).The results of receiver operating characteristic curve analysis showed that the sensitivity and specificity of the proportion of CD38+,HLA-DR+,Ki-67+PPD or ESAT-6/CFP-10 reactive CD154+CD4+T cells in differentiating smeg-positive patients were 59.62%to 86.54%and 72.92%to 91.67%,respectively.There was no statistically significant difference in the expression of CD38+,HLA-DR+and Ki67+in the smear-negative group before treatment and 2 months after treatment(P>0.05),but the proportion of MT-specific T cells of CD38+,HLA-DR+and Ki-67+in the smear-positive group decreased significantly 2 months after anti-tuberculosis treatment(P<0.05).Among smear-positive PTB patients,the proportions of CD38+,HLA-DR+and Ki-67+MT-specific CD154+CD4+T cells in the sputum non-negative conversion group after 2 months of treatment were significantly higher than those in the sputum negative conversion group(P<0.05).Moreover,the decrease amplitudes of the proportions of CD38+,HLA-DR+and Ki-67+MT-specific CD154+CD4+T cells in the group without sputum turning negative were significantly lower than those in the group with sputum turning negative(P<0.05).Conclusion The expression of MT-specific CD154+CD4+T cell activation and proliferation markers CD38,HLA-DR,and Ki-67 is helpful to distinguish sputum smear-negative and smear-positive PTB and monitor the anti-tuberculosis treatment response of smear-positive PTB patients.